Abstract Reciprocal connections between primate dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices, furnished by subsets of layer 3 pyramidal neurons (PNs), contribute to cognitive processes including working memory (WM). A different subset of layer 3 PNs in each region projects to the homotopic region of the contralateral hemisphere. These ipsilateral (IP) and callosal (CP) projections, respectively, appear to be essential for the maintenance and transfer of information during WM. To determine if IP and CP layer 3 PNs in each region differ in their transcriptomes, fluorescent retrograde tracers were used to label IP and CP layer 3 PNs in the DLPFC and PPC from macaque monkeys. Retrogradely-labeled PNs were captured by laser microdissection and analyzed by RNAseq. Numerous differentially expressed genes (DEGs) were detected between IP and CP neurons in each region and the functional pathways containing many of these DEGs were shared across regions. However, DLPFC and PPC displayed opposite patterns of DEG enrichment between IP and CP neurons. Cross-region analyses indicated that the cortical area targeted by IP or CP layer 3 PNs was a strong correlate of their transcriptome profile. These findings suggest that the transcriptomes of layer 3 PNs reflect regional, projection type and target region specificity.
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Refinement of the Primate Corticospinal Pathway During Prenatal Development
Abstract Perturbation of the developmental refinement of the corticospinal (CS) pathway leads to motor disorders. While non-primate developmental refinement is well documented, in primates invasive investigations of the developing CS pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. Here, we investigated the developmental changes in the distribution of CS projection neurons in cynomolgus monkey (Macaca fascicularis). Injections of retrograde tracer at cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that: (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal, and occipital cortex; (ii) distributions of contralateral and ipsilateral projecting CS neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter. In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus, and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.
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- Award ID(s):
- 1724297
- NSF-PAR ID:
- 10211674
- Date Published:
- Journal Name:
- Cerebral Cortex
- ISSN:
- 1047-3211
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The development of the ability to anticipate—as manifested by preparatory actions and neural activation related to the expectation of an upcoming stimulus—may play a key role in the ontogeny of cognitive skills more broadly. This preregistered study examined anticipatory brain potentials and behavioral responses (reaction time; RT) to anticipated target stimuli in relation to individual differences in the ability to use goals to direct action (as indexed by measures of executive function; EF). A cross‐sectional investigation was conducted in 40 adults (aged 18–25 years) and 40 children (aged 6–8 years) to examine the association of changes in the amplitude of modality‐specific alpha‐range rhythms in the electroencephalogram (EEG) during anticipation of lateralized visual, tactile, or auditory stimuli with inter‐ and intraindividual variation in RT and EF. Children and adults exhibited contralateral anticipatory reductions in the mu rhythm and the visual alpha rhythm for tactile and visual anticipation, respectively, indicating modality and spatially specific attention allocation. Variability in within‐subject anticipatory alpha lateralization (the difference between contralateral and ipsilateral alpha power) was related to single‐trial RT. This relation was more prominent in adults than in children, and was not apparent for auditory stimuli. Multilevel models indicated that interindividual differences in anticipatory mu rhythm lateralization contributed to the significant association with variability in EF, but this was not the case for visual or auditory alpha rhythms. Exploratory microstate analyses were undertaken to cluster global field power (GFP) into a distribution‐free temporal analysis examining developmental differences across samples and in relation to RT and EF. Anticipation is suggested as a developmental bridge construct connecting neuroscience, behavior, and cognition, with anticipatory EEG oscillations being discussed as quantifiable and potentially malleable indicators of stimulus prediction.
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Key points Motor units, comprising a motor neuron and the muscle fibre it innervates, are activated in an orderly fashion to provide varying amounts of force.
A unilateral C2 spinal hemisection (C2SH) disrupts predominant excitatory input from medulla, causing cessation of inspiratory‐related diaphragm muscle activity, whereas higher force, non‐ventilatory diaphragm activity persists.
In this study, we show a disproportionately larger loss of excitatory glutamatergic innervation to small phrenic motor neurons (PhMNs) following C2SH, as compared with large PhMNs ipsilateral to injury.
Our data suggest that there is a dichotomy in the distribution of inspiratory‐related descending excitatory glutamatergic input to small
vs . large PhMNs that reflects their differential recruitment.Abstract Excitatory glutamatergic input mediating inspiratory drive to phrenic motor neurons (PhMNs) emanates primarily from the ipsilateral ventrolateral medulla. Unilateral C2 hemisection (C2SH) disrupts this excitatory input, resulting in cessation of inspiratory‐related diaphragm muscle (DIAm) activity. In contrast, after C2SH, higher force, non‐ventilatory DIAm activity persists. Inspiratory behaviours require recruitment of only smaller PhMNs, whereas with more forceful expulsive/straining behaviours, larger PhMNs are recruited. Accordingly, we hypothesize that C2SH primarily disrupts glutamatergic synaptic inputs to smaller PhMNs, whereas glutamatergic synaptic inputs to larger PhMNs are preserved. We examined changes in glutamatergic presynaptic input onto retrogradely labelled PhMNs using immunohistochemistry for VGLUT1 and VGLUT2. We found that 7 days after C2SH there was an ∼60% reduction in glutamatergic inputs to smaller PhMNs compared with an ∼35% reduction at larger PhMNs. These results are consistent with a more pronounced impact of C2SH on inspiratory behaviours of the DIAm, and the preservation of higher force behaviours after C2SH. These results indicate that the source of glutamatergic synaptic input to PhMNs varies depending on motor neuron size and reflects different functional control – perhaps separate central pattern generator and premotor circuits. For smaller PhMNs, the central pattern generator for inspiration is located in the pre‐Bötzinger complex and premotor neurons in the ventrolateral medulla, sending predominantly ipsilateral projections via the dorsolateral funiculus. C2SH disrupts this glutamatergic input. For larger PhMNs, a large proportion of excitatory inputs appear to exist below the C2 level or from contralateral regions of the brainstem and spinal cord.
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Abstract Vocal learning in songbirds is mediated by cortico‐basal ganglia circuits that govern diverse functions during different stages of development. We investigated developmental changes in axonal projections to and from motor cortical regions that underlie learned vocal behavior in juvenile zebra finches (
Taeniopygia guttata ). Neurons in LMAN‐core project to RA, a motor cortical region that drives vocal output; these RA‐projecting neurons send a transient collateral projection to AId, a region adjacent to RA, during early vocal development. Both RA and AId project to a region of dorsal thalamus (DLM), which forms a feedback pathway to cortico‐basal ganglia circuitry. These projections provide pathways conveying efference copy and a means by which information about vocal motor output could be reintegrated into cortico‐basal ganglia circuitry, potentially aiding in the refinement of juvenile vocalizations during learning. We used tract‐tracing techniques to label the projections of LMAN‐core to AId and of RA to DLM in juvenile songbirds. The volume and density of terminal label in the LMAN‐core→AId projection declined substantially during early stages of sensorimotor learning. In contrast, the RA→DLM projection showed no developmental change. The retraction of LMAN‐core→AId axon collaterals indicates a loss of efference copy to AId and suggests that projections that are present only during early stages of sensorimotor learning mediate unique, temporally restricted processes of goal‐directed learning. Conversely, the persistence of the RA→DLM projection may serve to convey motor information forward to the thalamus to facilitate song production during both learning and maintenance of vocalizations. -
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The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory nuclei. Prominent projections of individual MNTB neurons comprise the major binaural nuclei that are involved in the early processing stages of sound localization as well as the superior paraolivary nucleus (SPON), which contains monaural neurons that extract rapid changes in sound intensity to detect sound gaps and rhythmic oscillations that commonly occur in animal calls and human speech. While the processes that guide the development and refinement of MNTB axon collaterals to the binaural nuclei have become increasingly understood, little is known about the development of MNTB collaterals to the monaural SPON. In this study, we investigated the development of MNTB-SPON connections in mice of both sexes from shortly after birth to three weeks of age, which encompasses the time before and after hearing onset. Individual axon reconstructions and electrophysiological analysis of MNTB-SPON connectivity demonstrate a dramatic increase in the number of MNTB axonal boutons in the SPON before hearing onset. However, this proliferation was not accompanied by changes in the strength of MNTB-SPON connections or by changes in the structural or functional topographic precision. However, following hearing onset, the spread of single-axon boutons along the tonotopic axis increased, indicating an unexpected decrease in the tonotopic precision of the MNTB-SPON pathway. These results provide new insight into the development and organization of inhibition to SPON neurons and the regulation of developmental plasticity in diverging inhibitory pathways.
SIGNIFICANCE STATEMENT The superior paraolivary nucleus (SPON) is a prominent auditory brainstem nucleus involved in the early detection of sound gaps and rhythmic oscillations. The ability of SPON neurons to fire at the offset of sound depends on strong and precise synaptic inhibition provided by glycinergic neurons in the medial nucleus of the trapezoid body (MNTB). Here, we investigated the anatomic and physiological maturation of MNTB-LSO connectivity in mice before and after the onset of hearing. We observed a period of bouton proliferation without accompanying changes in topographic precision before hearing onset. This was followed by bouton elimination and an unexpected decrease in the tonotopic precision after hearing onset. These results provide new insight into the development of inhibition to the SPON.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/cercor/bhz116
